HBOT: MECHANISMS OF ACTION - TreatNOWtreatnow.org/wp-content/uploads/2015/10/How-HBOT-Works-2.pdf · 2015-10-27 · Harch PG. Application of HBOT to acute neurological conditions.

HBOT: MECHANISMS OF ACTION

HBOT’s mechanisms of action are well known and well

characterized both in scientific literature and in clinical practice.

Translational Medicine Methods are Necessary to make these treatments for these conditions ROUTINE!

Typical Multiplace Hyperbaric Chamber

Hyperbaric Medicine has been used for 75 years to treat brain insults!

HBOT is approved and on-label for 13 indications and treatment is reimbursed by all major third party payers including Medicare, Tricare and the Veterans Administration.

Typical Monoplace Hyperbaric Chamber

Hyperbaric oxygen therapy is the only non-hormonal treatment approved by the FDA for biologically repairing and regenerating human tissue.

It is FDA-approved and effective for the treatment of 3 kinds of non-healing wounds. It is currently FDA-approved as the primary treatment for 3 different kinds brain

injuries: carbon monoxide poisoning, arterial gas embolism, and cerebral decompression sickness.

Hyperbaric Oxygen Therapy is not Black-Labeled by the FDA, as are many drugs currently being prescribed off-label for post-traumatic stress disorder or traumatic brain injury.

Copyright retained: Paul G. Harch, M.D., 2010 & IHMA

FDA Accepted HBOT Indications HBOT as used by the team is currently in use for 13 FDA-accepted indications (which means the

manufacturer or practitioner can advertize those indications) by hundreds of physicians at nearly 1,000 locations across the nation, delivering approximately 10,000 treatments per day.

The thirteen accepted indications for HBOT treatment include: 1. Air or gas embolism. 2. CO poisoning, CO poisoning complicated by cyanide poisoning (Neurological) 3. Clostridial myositis and myonecrosis (gas gangrene) 4. Crush injury, compartment syndrome, and other acute traumatic ischemias 5. Decompression sickness (Neurological)

6. Arterial Insufficiency: (Non-Healing Wound)

Enhancement of healing in selected problem wounds (includes uses like Diabetic Foot Wounds, Hypoxic Wounds, and other non-healing wounds, etc.)

7. Exceptional blood loss anemia 8. Intracranial abscess (Neurological) 9. Necrotizing soft tissue infections 10. Osteomyelitis (refractory) 11. Radiation tissue damage (soft tissue and bony necrosis) (Non-Healing Wound) 12. Skin grafts and flaps (compromised) (Non-Healing Wound) 13. Thermal burns[1]

[1] Hyperbaric Oxygen Therapy: 1999 Committee Report. Editor, N.B. Hampson. Undersea and Hyperbaric Medical Society, Kensington, MD. See also: Harch PG. Application of HBOT to acute neurological conditions. Hyperbaric Medicine 1999, The 7th Annual Advanced Symposium. The Adams Mark Hotel, Columbia, South Carolina, April 9-10, 1999; and Mitton C, Hailey D. Health technology assessment and policy decisions on hyperbaric oxygen treatment. Int J of Tech Assess in Health Care, 1999;15(4):661-70.

HBOT: It’s About Oxygen Saturation The body’s liquids are saturated with more oxygen, helping areas with compromised circulation.

After HBOT Before HBOT

Image Courtesy of Dr. Stoller

Solution: It’s Just Oxygen! HBOT: Oxygen is being used to repair an injury caused by a lack of oxygen!

• Simple: Lack of oxygen is bad

• O2 used in 5,769+ cellular processes

• HBOT activates 8,101 Genes! – Down Regulates Inflammation Processes

– Up Regulates Growth & Repair Processes

– Normobaric O2 does not!

• We know how HBOT works! – Acutely stops swelling/reperfusion injury

– Restarts stunned cellular metabolism

– Restarts Stunned Mitochondria

• Mitochondria then Request Oxygen (Blood Supply)

• Body Re-grows Blood Vessels

– Activates Stem Cells 8x Normal

• to repair neural pathways

• No wound can heal without oxygen – Wounds that have not healed do

– Wounds heal 50% faster with less scar tissue

– Broken bones 30% faster & 30% stronger

• Placebos have to have the potential of being inert. Saturating injured tissue with any dose

of oxygen has never been shown to have a placebo effect!

Pressure causes oxygen

to saturate tissues higher

than normal breathing:

HBAT 1.3: 30%* more O2

HBOT 1.5: 700% or 7x

HBOT 2.4: 1200% or 12x HBAT is Compressed Air & HBAT 1.3 is the FDA

Approved Treatment for Mountain Sickness

HBOT is FDA-approved & available & On-Label for

neurological conditions & non-healing wounds!

*25% more O2 in tissues is so clinically significant that DoD medicine

has spent millions in research trying to achieve it. It is already

available on the battlefield with mountain sickness chambers using air!

How Oxygen works - 5,769+* ways (~# of cellular processes studied)

• Upregulates growth factors

• Reduces edema/swelling

• Promotes neural pathway growth

• Activates senescent neurons [“sleeping”, not dead]

• Increases neuronal energy [ATP]

• Downregulates inflammation

• Reduces reperfusion injury [not enough O2]

*Rink C, Roy S, Khan M, Ananth P, Kuppusamy P, Sen CK, Khanna S. Oxygen-sensitive

outcomes and gene expression in acute ischemic stroke. J Cereb Blood Flow Metab.

2010 Feb 10.

HBOT: Its about the Mitochondria

Image Courtesy of Dr. Stoller

HBOT Acts on Mitochondria Restart Cellular Metabolism

• Brain Death is diagnosed and declared when there is no blood in the brain. - Why?

• The Brain is not asking for blood. Why?

• The various cells in the brain are not asking for blood. Why?

• Mitochondria are not asking for Oxygen

• Idling Neuron-Lancet Letter – Neurons become Dormant before

Death and can be reactivated by saturating body fluids with oxygen

• Dormant Cells have now been found throughout the body, from hearts to lungs.

Request for Oxygen Supply • Dormant or stunned neuron

mitochondria make 2 ATP

• HBOT Reactivated 36 ATP are made

• When Reactivated, mitochondria immediately begin requesting O2

• If O2 is not readily available because the blood supply has been compromised, DNA is signaled to start repair and grow a blood supply.

• HBOT-O2s Pulsed Dose in HBOT protocols keep the process going.

– Academic Medical Research has been focused on trying to force the blood supply into damaged areas

– The natural process repairs metabolism inside the cells, which then sends the repair signals out.

Source: Leo Germin, MD, Neurologist, Las Vegas, Nevada

HBOT works at the DNA level

• Decreases hypoxia-inducible factor-1a

(hip-1a) & multiple genes related to apoptosis

• Inhibition of apoptosis (programmed cell death) by HBOT translates into brain tissue preservation

Zhang, JH et al. Neuroscience and Critical Care Yin, W Brain Res 926: 165-171

Badr et al 2001 brain Res 916: 85-90 Atochin, DN 2000 UHMS 27: 185-190

Image Courtesy of Dr. Stoller

HBOT: It’s About Your Own Stem Cells

In humans, HBOT at 2.0 atm and 100% oxygen for 2

hours per treatment for 20 treatments increased the

number of circulating stem cells in the blood by 8-fold

Thom et al., 2006

Am J Physiol Heart Circ Physiol 290:1378-86

Image Courtesy of Dr. Stoller

Non-Healing Wound of the Foot Diabetic Foot Ulcer: This Wagner Grade III was present for one

year and unresponsive to conventional therapy.

26 HBOT Treatments

50 HBOT Treatments

Hyperbaric Oxygenation prevents 75% of amputations in diabetic patients. Therapy approved by CMS for Medicare upon application by IHMA to CMS for coverage, 2003.

These photographs are the property of Kenneth P. Stoller, MD, FAAP Permission given by Dr. Stoller to the IHMA to publish on this CD (2004)

1 Day Prior to Scheduled Amputation

Copyright retained: Kenneth Stoller, M.D., 2010 & IHMA

Pre-HBOT 1.5 Post-HBOT 1.5

Non-Healing Wound of the Brain Physical Abuse - 9 years after Injury - 21 y. female

No wound will heal without oxygen!

What is the difference between the diabetic non-healing foot wound and the non-

healing brain injury? Essentially nothing. FDA has already approved HBOT for

3 kinds of non-healing wounds and 3 neurological injuries!

Myth: “90% Recover from Brain Injury” “Recovery” does not mean “healed without residual effect”

or restoration to prior mental capabilities.

Acute Injury? Minutes Matter

71.3 m

12.8 min

5.2 min

Solution to Brain Injury: Biologically Repair the Brain

Case Published in: Cases Report June 2009 http://casesjournal.com/casesjournal/rt/suppFiles/6538/31370

Brain Insults often Result in a 50% Decrease In Brain Metabolism

HBOT Restores Brain Metabolism

Case Published in: Cases Report June 2009 http://casesjournal.com/casesjournal/rt/suppFiles/6538/31370

The Specific Science for HBOT 1.5 • 1977 Study: Holbach & Wasserman PMID: 75249 : HBOT 1.5 puts the most oxygen into the brain because more triggers an autonomic

response to keep extra O2 out! Chronic Stroke patients treated at numerous locations. • 1990: Harch treats first demented diver for delayed decompression sickness. Numerous small studies published. (See Memorandum) • 2002: US Army verifies HBOT 1.5 repairs white matter damage in children. ISSN1524-0436 • 2007: Rat HBOT 1.5 study for Chronic TBI published in Brain Research. Human protocol in Animals. First improvement of chronic brain

injury in animals in the history of science. PMID: 17869230 • August 14, 2008: Briefing to Surgeon General of the Navy & Deputy Commandant, US Marine Corps: 5 blast injured veterans treated.

All five made improvements, some dramatic. Four of five were able to return to duty or civilian employment! First Case was Published April 2009 PMID: 19829822 [PubMed]

• September 2008: US Air Force Hyperbaric Researcher & Special Forces Command Physician treats two airmen. Results verified by ANAM neuropsych test. Both are restored to duty saving the Federal government an estimated $2.6 million each in lifetime costs. They continue their careers. More active duty personnel are treated. Published in January, 2010 in Peer Reviewed Journal (PMID: 20112530) (See Research www.HyperbaricMedicalFoundation.org)

• March 12, 2010: Report on 15 Blast Injured Veterans under LSU IRB-approved study. Report is clinically and statistically significant and sufficient proof because of dramatic improvement in patients. ½ of protocol given (WBIC0653)

– 15 point IQ jump in 30 days p<0.001, 40% improvement in Post-concussion symptoms p=0.002 (np), (10% is considered clinically significant enough to warrant approval and payment for HBOT according to DoD researchers in December 2008.)

– 30% reduction in PTSD symptoms p<0.001, 51% Reduction in Depression Indices p<0.001

• NBIRR-01 Begins Enrolling Patients March 2010. Preliminary Results from multi-site study support Harch’s Findings.

• LSU Pilot Published in the Journal of Neurotrauma, J Neurotrauma. 2011 Oct 25. A Phase I Study of Low Pressure Hyperbaric

Oxygen Therapy for Blast-Induced Post Concussion Syndrome and Post Traumatic Stress Disorder PMID: 22026588

– Subjects as a group showed significant improvements on most measures of intelligence, function and quality of life

– All subjects received 1/2 the clinically recommended protocol being used in NBIRR-01 (NCT01105962)

– Nearly 15 point IQ Increase (average) (Difference between a high school dropout & a college graduate)(14.8 P<.001 )

– Post-Concussion Syndrome (PCS): 39% Reduction in PCS symptoms (p=0.0002); 87% substantial headache reduction

– 30% Improvement in PTSD (20 points of a 85 point scale; 10% is considered clinically significant)

– 51% Reduction in Depression Indices with Large Reduction in Suicide Ideation(p=0.0002)

– 64% had a reduced need for psychoactive or narcotic prescription medications

– 100% showed sustained improvement on neuropsychological tests 6 months post treatment

– Functional Improvements: Cognitive 39% (p=0.002); Physical 45% (p<0.001); Emotional 96% (p<0.001) • Significant Reduction in Anger Issues!

– Placebo Effect Ruled Out! Results too great to be placebo effect and neurological imaging is inconsistent

with a placebo effect

HBOT 1.5 Provided the Largest Published Reduction in PTSD

• LSU Pilot Study: 30% Reduction

• Cognitive Processing Therapy [TAU]: 14% or 4.8% -Chard, 2011 & Alvarez 2011

• Trauma Focused Group Treatment [TAU]: 2.2%

• Prolonged Exposure Therapy [PE]: 28% -Wolf, 2012

• Transcendental Meditation [TM]: 21% -Rosenthal, 2011

• Virtual Reality Exposure Therapy [VRET]: 23% – Rizzo, 2011

Note: All results are time adjusted for the length of treatment in the LSU study

HBOT is Rapidly Deployable • Note the Level of Education needed for health care

professional providing treatment in the previous slide.

– Subjects in other therapies had a Masters or Ph.D. or Physician level therapist.

• HBOT can be delivered by a health care provider with EMT level 1 or better training, with overall physician supervision.

• Thus HBOT is more readily deployable, a lower strain on resources, and more effective than any other published therapy.

IHMF Is Solving the TBI/PTSD Problem • The Challenge is Getting Paid for Treatment So We

can Restore People’s lives! – State Medicaid Rules Restrict Treatment Locations

– Payment is NOT made even when patients recover! (HR396 will help)

• No Other Such Clinic Treatment Network Exists! • Our Team Leaders have decades of experience with Hyperbaric Medicine

– Our Team Leaders have over 20 years of experience treating Brain Injury & restoring lives with this protocol

– The NBIRR-01 Study is IRB-approved and is Listed at www.ClinicalTrials.gov

• Public Officials can send case work for treatment

• Public officials & Judges can put individuals on a path to treatment

– The National Call Center Number is: (800) 288-9328

• TODAY IHMF is Helping to Solve the Real Problems of Brain Injured Persons with Biological Repair for their Injury

0

10

20

30

40

50

60

70

80

90

100

Simple Reaction Time Procedural Reaction

Time

Code Substitution

Learning

Code Substitution

Delayed

Mathematical

Processing

Matching to Sample

Airman B ANAM Percentile Scores

11-Nov-07 21-Jul-08 10-Oct-08 16-Jan-09

Pre-Deployment Post-Deployment 40 HBOT 1.5s 80 HBOT 1.5s

Figure 1: The passenger side of the M915 truck showing the damage caused by the IED.

Conclusion by article authors:

Several aspects of these two cases demonstrate the efficacy of HBO for the airmen treated. Although both airmen had stable symptoms of mTBI/post-concussive syndrome, which had not improved for seven months; substantive improvement was achieved within ten days of HBO treatment. The headaches and sleep disturbances improved rapidly while the irritability, cognitive defects, and memory difficulties improved more slowly.

Fortunately both airman had taken the ANAM and presented objective demonstration of their deficits from TBI and their improvements after HBO treatment. Both airmen, who were injured by the same blast sitting side by side, had similar symptom complexes of TBI and improved at similar rates after initiation of HBO treatment. Neither airman had any other form of treatment for TBI. It seems unlikely to the authors that any explanation other than the HBO treatments can be

offered for their improvements.

“Case report: Treatment of Mild Traumatic Brain Injury with Hyperbaric Oxygen: Colonel James K. Wright, USAF, MC, SFS; Eddie Zant, MD; Kevin Groom, PhD; Robert E. Schlegel, PhD, PE; Kirby Gilliland, PhD”

ANAM Scores - pre-injury, post-injury, after HBOT Budget Savings from Restoring 4 Military Personnel to Duty: $11.2 million

Long Term Additional Savings: $8 million ($19.2 million) Cost? $96,000

100%

50%

0

Confidentiality Statement applies.

Severe TBI Patient: Whole Brain CT Perfusion Pre & Post HBOT

Pre HBOT – 10/16/09 Post HBOT – 10/28/09

Images Courtesy of Dr. Germin, Las Vegas

Fractures

• Dr. Wright’s Air Force Research Demonstrated that Fractures heal 30% faster and 30% stronger when Hyperbaric Oxygen is used.

– Shorter back to work time

– Stronger Fusion

• Cost Effective through reduced down time

The effect of hyperbaric oxygen on fracture healing in rabbits, completed 2003. J Wright

Is Hyperbaric Medicine Safe? Source: “HBOT for TBI” Consensus Conference, December 2008

• Treatment involves simply breathing pure oxygen under pressure (often while sleeping or watching TV).

• Ten thousand plus similar treatments are given every day at 1,200+ locations nationwide for other indications.

• The DoD White Paper stated: “side effects are uncommon and severe or permanent complications are rare…” (White Paper for the

HBOT in TBI Consensus Paper, 12/08)

• The DoD After Action Report stated: “safety of the treatment is not an issue.” (After Action Report HBOT in TBI

Consensus Conference, Defense Centers of Excellence, 16 Dec 2008)

Examples: HBOT is Synergistic with Other Treatments

• Drug Protocols

– Patients in the LSU Study were on no medication or less medication

– Medication was now more effective at controlling remaining symptoms

• Nutritional Programs

– NBIRR Nutritional Program reduced Aberrant Violent Behavior in Felons in 30 RCT Studies by 39-41%

– Harch did not use NBIRR supplement in his study

• Cognitive Rehabilitation

– Treatment Cannot Begin until a Patient can Sleep Through the Night

– HBOT Repairs Sleep Cycles and most Patients can begin sleeping at 10 HBOT Treatments

– When Brain Tissue is Recovered, it is somewhat disorganized!

• Acupuncture

• Bio-Feedback

• Counseling & Coping Skills

Micro Air Embolism Contribution to Blast-Induced Mild Traumatic Brain Injury Reimers, SD1; Harch, PG2; Wright, JK3; Slade, JB4; Sonnenrein, R1; Doering, ND1

1Reimers Systems, Inc., Lorton VA; 2 Clinical Associate Professor and Director; Wound Care and Hyperbaric Medicine Department, LSU School of Medicine, New Orleans, LA; 3Col., USAF MC (ret.), Butte MT; 4Baromedical Associates, Doctors Medical Center, San Pablo CA

INTRODUCTION

Massive air embolism (AE) from lung disruption is the accepted principal etiology of mortality in

blast injury (White et al., 1971; Sharpnack, Johnson & Phillips, 1990). For sub-lethal blast injury,

air embolism has been ignored, considered innocuous or believed to have not occurred. The

high incidence of post-concussion syndrome (PCS), neurocognitive deficits, and mental health

issues resulting from sub-lethal blast injuries in U.S. Iraq and Afghanistan War veterans has

vexed military authorities and medical specialists. We propose that micro air embolism is a

heretofore unappreciated etiologic factor.

MATERIALS AND METHODS

Materials and Methods: Using PubMed, PsychInfo, Google Scholar, Sci.gov, and PubCrawler, a

systematic review of the literature was conducted identifying published papers in the following

domains: biodynamics and physics of blast overpressure; primary blast injury; microbubbles in

systemic circulation from diving and iatrogenic causes; neurological problems and microbubbles.

When necessary, key documents were obtained from U.S. Government archives. Reference lists

of articles were also scanned. Papers with both significant and null findings were included.

RESULTS

Blast-induced AE

• For mammals that die promptly from either air or underwater blast, air embolism has long been

recognized as the primary cause of death (Desaga,1950; Shapnack, Johnson & Phillips, 1990;

Richmond & Damon, 1991). Lung disruption is proportional to both magnitude and length of

blast overpressurization (Buamoul, 2009) with disruption beginning to occur at modest

overpressures easily within the range of pressures experienced by U.S. combat troops from

improvised explosive devices (IED) (Fig 1 & 3).

• The disruption threshold is lowered by exposures near reflective surfaces, exposures inside

structures that impede dispersion of the blast gases, and by longer exposure times. It is further

lowered by repeat exposures in less than 24 hours (Stuhmiller, Phillips & Richmond, 1990).

• Benzinger (1950) concluded that because symptoms were only present when a blast hit the

thorax, air embolism must originate in the thorax and becomes effective when it travels to the

brain. Benzinger also found that small amounts of air in arterial circulation could readily

reproduce neurologic symptoms seen in blast injury to dogs and humans. Only 1 cc of air

injected into the pulmonary veins of a dog was sufficient to reproduce the electrocardiographic

changes seen in blast-injured dogs (Phillips & Richmond, 1990).

• Maison (1971) outfitted a dog with a Doppler bubble detector on the carotid artery, exposed

the dog to an LD50 air blast, and subsequently observed bursts of Doppler deflections going

up the carotid correlating with respirations for approximately 30 minutes post-blast. The dog’s

carotid blood flow was observed to temporarily drop to near zero following each group of

echoes, possibly indicating reduced blood velocity due to temporary distal occlusions (Fig. 2).

The dog initially showed severe respiratory distress, but recovered. Postmortem exam showed

evidence of residual lung hemorrhage, but no other damage. Maison concluded that the

bubbles were “clinically silent”.

• A conceptual model of how AE sequelae to blast exposure occurs, confirmed with rabbit

model data, can be found in White (1971). Any fast-rising blast pressure wave long enough to

produce significant chest compression is likely to produce some AE.

• Goh (2009) and Mayo & Kleger (2006) in separate articles regarding civilian blast casualty

management advise that AE is a possible complication of exposure to air blast. However,

neither author addresses the possibility of neurocognitive sequelae from AE.

• Protective vests reduced mortality & neural fiber degeneration in rats exposed to air blast

(Long, et.al., 2009)

Evidence that microbubbles are NOT harmless

• Microbubbles were first recognized as a medical hazard in open-heart surgery decades ago

(Barak & Katz 2005). Air emboli from various sources in the extracorporeal circulation (ECC)

set and tubes can drift into the aorta and systemic circulation, carrying microbubbles to the

brain. Clinical results of this unwanted event include major and minor neurologic injury,

neurocognitive deterioration and an overall general decline in patient health (Barak, Nakhoul &

Katz, 2008; Shaw et al., 1987). The degree of decline in cognitive performance has been

correlated to the amount of air emboli delivered during the ECC (Deklunder et al., 19981,2).

Patients with neuropsychological deficits 5 to 7 days after coronary bypass graft surgery

averaged nearly twice the number of emboli compared to those without deficits (Stump, et al.,

1996).

• In mechanical heart valve carriers, bubbles are chronically delivered into the arterial system at

variable rates, which can rise as high as 800 per hour in the cerebral circulation. Patients with

these devices have been found to have impairment in episodic memory and deficits in working

memory (Deklunder et al., 19981,2).

• Multiple brain lesions in divers with no reported history of neurological DCS have been found

to be strongly correlated with patent foramen ovale of high haemodynamic relevance. This

finding lead the authors to a hypothesis that the brain lesions were the consequence of

subclinical cerebral gas embolism (Knauth et al., 1997).

• A review of 140 cases of delayed DCS treatment (avg. delay 93.5 hrs) reported findings of

neurocognitive symptoms including severely reduced executive function, apathy and antisocial

behavior in 49% of the patients. 100% of the neurocognitive symptoms resolved with

hyperbaric oxygen therapy. (HBOT) (Cianci & Slade, 2006).

• In hemodialysis, CNS abnormalities attributed to microbubbles have been correlated with the

duration of dialysis treatment. Barak & Katz (2008) attributed the abnormalities to

microbubbles and stated “a small quantity of microbubbles may be clinically silent, while

recurrent exposure has a slow, smoldering, chronic effect” (p. 2921)

Recent Combat Medical Literature

• Bauman et al. (2009) provides a summary of the test conditions and initial results from the

PREVENT (Preventing Violent Explosive Neurotrauma) research program being conducted

by DARPA. In the tests reported (swine model), the thorax and upper abdomen were

protected to minimize the possibility of brain injury by indirect pathways. Some neurological

damage was observed, and its significance is still being determined. However, the test

conditions are of interest as they are also ones where lung injury can readily occur. Point C

on Fig. 1 represents a typical Friedlander wave reported for the blast tube. Test set-ups were

built to simulate exposures in the crew compartment of a Humvee with a blast under its floor

and an open gunner port and in semi-confined space (open top room with dimensions as

shown in Fig 1). In both cases the overpressure durations from a moderate sized charge

were reported to be about 4 ms. The overpressure data was reported in general form only

without numerical values. However, at 4 ms duration, the pressures required to produce lung

injury are not large. In situations where the Humvee or building were to be fully closed, both

the magnitude and duration of blast overpressures can be expected to be greater.

• Buamoul (2009) reports results from a computer model developed by Defence R & D

Canada (CRDC) for estimating the blast damage to the lungs of sheep and humans. He

reports the intra-thoracic pressure range currently accepted as the “threshold” for lung

damage is 70 kPa (695 cmH20) to 110 kPa (1,091 cmH20), which corresponds roughly to the

intra-thoracic pressures predicted by the model at exposures near the lung damage threshold

line on the Bowen charts. The intra-thoracic pressures produced by even moderate size

blasts can be very substantial (Fig. 3). They also vary widely with both time and location in

the lung, suggesting that opportunities for localized AE may be plentiful. The model also

indicates that complex (multi-peak) blast waves can produce higher lung pressures, and

therefore greater risk of lung damage than do single peak, classic Friedlander waves of the

same impulse value.

• Recent work by Yang et al.,1996 (sheep model) suggests the lung damage threshold

pressure may be as much as 75% lower than the Bowen charts (Fig 1) indicate when

the threshold pressure is taken as the lowest pressure at which lung tissue damage is

observable by light and/or electron microscopy.

Available literature suggests that transient AE from primary blast exposure is possible, perhaps

probable, at sub-lethal overpressures similar to the overpressures experienced by U.S. combat

Veterans. Arterial microbubbles have been shown to be neurologically harmful and may

contribute to the high incidence of post-concussion syndrome in blast injured veterans. Current

research efforts are almost exclusively focused on the direct cerebral effects of blast waves. The

AE pathway deserves prompt and thorough investigation.

Fig. 1: Blast Waves Are More Than Simple Shock Waves, Duration Makes a Difference RESULTS (CON’D)

Copyright: Reimers Systems, Inc. 2011, All rights

reserved.

Notes to Fig. 1

1.Figure is based on the survival curves for a 70 kg man where the thorax is near a surface against which a blast wave reflects at

normal incidence (Bowen, Fletcher, & Richmond,1968). data shown is for a single reflection where the total overpressure is ~2x

incident pressure. Total pressures can be up to 8x incident pressure if circumstances are right (Richmond & Damon,1991). In f ree

field exposures (no reflections) the damage thresholds are approx. 2x those shown. When used, free field pressure data values are

plotted at 50% of actual.

2. “Short” and “Long” refer to the ratio of the length of the overpressure region to thorax dimensions. Long blast waves produce much

greater chest compression (White et al., 1971).

3. Repeat exposures in less than 24 hours, lower the lung damage threshold (Stuhmiller, Phillips & Richmond 1990).

4.The lung damage threshold curve is based on an estimated damage threshold of 20% of the 50% mortality level (White et al.,

1971). Recent data (Yang et al., 1996) suggests the threshold pressures for lung damage may be lower (circa 50%) than those

shown.

5.Blast waveform is also important. However, that is beyond what can be addressed in this poster.

6.A = shock wave period, B= period where expanding blast gases maintain compartment pressure • It is well established that AE is a possible/probable sequelae of exposure to air blast.

• It is also well established that microbubbles are harmful to brains, and that symptoms may

not manifest immediately.

• Blast overpressure exposures typical of the current wars in Iraq and Afghanistan, particularly

blast exposures in confined spaces, are sufficient to create risk of lung damage. Quickly

repeated exposures increase the risk.

• It is reasonable to expect that the degree of blast-related AE is a continuum ranging from no

bubbles, to a few microbubbles to massive amounts depending on the exposure.

• The blast-related intra-thoracic pressures can be very substantial (Fig 3). The range

customarily accepted as the threshold for lung injury is 7 to 11 times higher than the 80

mmHg (10.7 kPa) differential known to produce disruption of aveolar-capilary boundary

tissues in slowly varying pressure environments such as diving (Neuman, 1997).

• Work by Yang, et. al (1996) suggests that lung tissue damage, and the concurrent possibility

of transient microbubble release, can occur at lung damage levels insufficient to produce

clinical blast lung and at overpressures substantially lower than indicated by the widely-used

Bowen charts.

• The CRDC model confirms suggestions from prior efforts that complex blast waves typical of

confined space exposures are more likely to be damaging to lungs than are the simpler

waveforms typical of free-field blasts.

• Blast related bubble production, when it does occur, has been shown to be transient, lasting

only 15 minutes to 3 hours for significant AE (Mayo & Kluger, 1996). The duration of

microbubble production can be expected to be shorter still making them hard to detect.

• All recent publications that we found, including a recent review article (Cernak & Noble,

2009), were silent on the possible role of microbubbles as a mechanism for blast-related

brain injury.

• When all the factors that may favor microbubble production are considered, it is difficult to

expect they do not occur.

• Undetected arterial microbubbles have the potential to significantly confound research into

other mechanisms of blast-related brain injury. In research studies where there is a

possibility of microbubble production, monitoring for their occurrence is

recommended.

The contribution of micro air embolism to blast-related brain injury may be

significantly greater than has been previously believed.

Fig. 2 Blood Velocity & Embolus Indications Following Canine Exposure to LD50 Air

Blast

7. Based on a wave speed of Mach 1. Most blast

waves are faster (up to Mach 2+) increasing the

wave length for the same time..

(Note 7)

Fig. 3 . Lung Injury Prediction from CRDC Model

Notes to Fig 3.

1. Data shown are peak intro-thoracic pressures and

lung damage estimates for a complex (2-peak) wave with a total impulse considered “threshold” for lung

damage in a free field (Point D in Fig. 1)

2. Data from Yang, et.al (1996) suggests the threshold

for “Trace” damage may be significantly lower that

assumed by the CRDC model.

Types of Hyperbaric Chambers